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Paola Arlotta
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- 69
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- 2019-08-12
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- 2019-08-12
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“And it was always thought that in order to build a big brain, a big nervous system, in order to have a nervous system that can do very complex type of things, then you need a lot of myelin because you want to go fast with this information from point A to point B. Well, a few years ago, maybe five years ago or so, we discovered that some of the most evolved, which means the newest type of neurons that we have as non-human primates, as human beings in the top of our cerebral cortex, which should be the neurons that do some of the most complex things that we do, well, those have axons that have very little myelin.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“So that's the most sort of canonical and definitely that's the case. So you have to imagine an axon and you can think about it as a cable of some type with electricity going through. And what Milin does by insulating the outside, I should say there are tracts of myelin and pieces of axons that are naked without myelin. And so by having the insulation, the electricity instead of going straight through the cable, it will jump over a piece of myelin, right, to the next naked little piece and jump again and therefore that's the idea that you go faster”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“The accents that call thexons exactly. And so As human beings, we might alienate ourselves postnatally, a kid, a six-year-old kid has barely started the process of making the mature oligodendrocytes, which are the cells that then eventually will wrap the axons into myelin. And this will continue, believe it or not, until we are about 25, 30 years old. So there is a continuous process of maturation and tweaking and additions. And also in response to what we do.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“This continuous way longer than just the first few months. So over the very first few months, you build a lot of these cells, but then there is continuous building of new cell types all the way through birth. And then even postnatalally, I don't know if you've ever heard of myelin. Myelin is this sort of insulation that is built around the cables of the neurons so that the electricity can go really fast from.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Are a lot of possibilities, right? And if you think about, for example, different species building their brain, each brain is a little bit different. So the brain of a lizard is very different from that of a chicken, from that of a one of us and so on and so forth and still is a brain, but it was built differently starting from stem cells that pretty much had the same potential. In the end, evolution builds different brains in different species because that serves in a way the purpose of that species and the well-being of that organism. So there are many possibilities, but then there is a way, and you were talking about a code. Nobody knows what the entire code of development is. Of course we don't. We know bits and bits and pieces of very specific Aspects of”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Yes, so if you use processes of development, then when you watch it, you can see that sometimes things can go wrong in some organoids. And by wrong, I mean different one organoid from the next. While if you think about that embryo, it always goes right. So this development, it's for as complex as it is. Every time a baby is born has, with very few exceptions, the brain is like the next baby. But it's not the same if you develop it in a dish. And first of all, we don't even develop a brain, you develop something much simpler in the dish. But there are more options for building things differently, which really tells you that evolution has played a really tight game here For how in the end the brain is built in vivo.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“They are much more prone to taking alternative routes, right? So if you Go back to printing a brain versus developing a brain. Of course, if you print a brain, given that you start with the same building blocks, the same cells, you could potentially print it the same way every time. But that final brain may not work the same way as a brain built during development does because very same building blocks that you're using developed in a completely different environment that was not the environment of the brain. Therefore, they're going to be different just by definition. So, if you instead use development to build, let's say, a brain organoid, which maybe we will be talking about in a few minutes.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Millions of years of evolution, of really fine tuning gene expression programs that allow certain cells to be made at a certain time and to become a certain cell type, but also mechanical forces of pressure bending. This embryo is not just, it will not stay a tube, this brain for very long. At some point, this tube in the front of the embryo will expand to make the primordium of the brain, right? Now the forces that control the cells feel, and this is another beautiful thing, the very force that they feel, which is different from a week before, a week ago, will tell the cell, oh, you're being squished in a certain way, begin to produce these new genes because now you are at the corner or you are in a stretch of cells or whatever it is. And so that mechanical physical force shapes the fate of the cell as well.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“First of all, thank you for saying that it's really the formation of the brain. It's really its development, it's this incredibly choreographed dance that happens the same way every time each one of us builds the brain, right? And that builds an organ that allows us to do what we're doing today, right? That is mind blowing, and this is why developmental neurobiologists never get tired of studying that. Now you're asking about the code. What drives this? How is this done? Well, it's.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Oh yes, if you are an engineer and you think about development, you can think of it as, well, I could also take all the cells and print them all together into a brain in the end. But development is much more than that. So the cells are made in a very specific order that subserve the final product that you need to get. And so, for example, all of the nerve cells, the neurons are made first, and all of the supportive cells of the neurons like the glia is made later. And there is a reason for that, because they have to assemble together in specific ways. But you also may say, well, why don't we just put them all together in the end? It's because as they develop next to each other, they influence their own development. So it's a different thing for a glia to be made alone in a dish than a glia cell be made in a developing embryo with all these other.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“And then with time, these progenitors become more heterogeneous, which means more diverse. There are going to be many different types of these stem cells. And also they will give rise to progeny, to other cells that are not stem cells, that are specific cells of the brain that are very different from the mother stem cell. And now you think about this process of making cells from the stem cells over many, many months of development for humans. And what you're doing, you're building the cells that physically make the brain, and then you arrange them in specific structures that are present in the final brain. So you can think about the embryonic development of the brain as the time where you're building the bricks, you're putting a bricks together to form buildings, structures, regions of the brain, and where you make the connections between these many different”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“A very good question is exactly how it works. You start with a more homogeneous, perhaps more multipotent type of stem cell. Multiportant, it means that it has the potential to make many, many different types of other cells.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“And then over in human beings over many months of gestation from that neural tube, which contains stem cell-like cells of the brain, you will make many, many other building blocks of the brain. So all of the other cell types, because there are many, many different types of cells in the brain, that will form specific structures of the brain. So you can think about embryonic development of the brain as just the time in which you are making the building blocks, the cells.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“In the embryo As the embryo is developing in the womb, in addition to making all of the other tissues of the embryo, the muscle, the heart, the blood, the embryo is also building the brain. And it builds from a very simple structure called the neural tube, which is basically nothing but a tube of cells that spans sort of the length of the embryo from the head all the way to the tail, let's say, of the embryo.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Exactly. That is very important for us to get the brain we have and we can speculate for why that is. You know, it takes us a long time as human beings after we're born to learn all the things that we have to learn to have the adult brain. It's actually 20 years. Think about it from when a baby is born to when a teenager goes through puberty to adults. It's a long time.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“With that interesting, very intriguing, interesting observation is that the time that it takes for the human brain to be made, it's human time, meaning that for me and you, it took almost nine months of gestation to build a brain and then another 20 years of learning postnatal to get the brain we have today that allows us to this conversation. takes 20 days or so to For an embryo to be born. And so the brain is built in a much shorter period of time. And the beauty of it is that if you take mouse stem cells and you put them in a culture dish, The brain organoid that you get from a mouse is formed faster than if you took human stem cells and put them in the dish and let them make human brain organoid.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“You pretty much find yourself, you know, all the time. It's an amazing process. It's a process by which, by means that we don't fully understand, at the very beginning of embryogenesis, the structure called the neural tube literally self assembles. And it happens in an embryo and it can happen also from stem cells in a dish. And then from there, these stem cells that are present within the neural tube give rise to all of the thousands and thousands of different cell types that are present in the brain through time, right?”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Most importantly, I guess we know very little about how this process really happens. And there is a reason for that, actually multiple reasons for that. Most of what we know about how the mammalian brains or the brain of mammals develop comes from studying in labs other brains, not our own brain, the brain of mice, for example. But if I showed you a picture of a mouse brain and then you put it next to a picture of a human brain, they don't look at all like each other. So they're very different. And therefore, there is a limit to what you can learn about how the human brain is made by studying the mouse brain. There is a huge value in studying the mouse brain. There are many things that we have learned, but it's not the same thing.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, it has happened here, right, on this planet. Once. So that simply tells you that it could, of course, happen again other places. It's only a matter of probability what the probability that you would get a brain, like the ones that we have. Like the human brain. So, how difficult is it to make the human brain? It's pretty difficult.”
2019-08-12 · Lex Fridman Podcast · Paola Arlotta: Brain Development from Stem Cell to Organoid · IDENTIFIED FROM THE TRANSCRIPT · source